Effects of econazole nitrate on yeast cells and mitochondria.

The inhibitory effect of econazole nitrate on the growth of yeast Saccharomyces cerevisiae is proportional to the concentration of the product. It depends on the phase of culture and on the number of cells present at the moment of econazole addition into the medium. The most important inhibition is obtained in the exponential phase of growth with a low concentration of cells. It is enhanced with cells which were previously in contact with the product. There is no adaptation of the yeast toward increased concentrations of econazole. The product penetrates the cells and attaches first to particular fractions, later to soluble fractions. The highest concentration of econazole nitrate in cells lies in the mitochondria. No product of econazole metabolism by S. cerevisiae was uncovered. Econazole nitrate does not slow down the in vivo activities of mitochondrial enzymes (cytochrome c oxidase, succinate dehydrogenase and phenylalanyl-tRNA synthetase), but inhibits the biosynthesis of mitochondrial membrane enzymes without affecting that of the synthetase, a matrix enzyme.